PROJECT SUMMARY Familial hypercholesterolemia (FH) affects over one million Americans and increases the risk of cardiovascular disease (CVD) by as much as 20-fold. Although the use of statins can substantially reduce this risk, adherence to statins in adults and adolescence is poor. In adults, lower rates of adherence are associated with an increased rate of CVD events and all-cause mortality, as well as an additional $44 billion annually in health care costs. Novel interventions are needed to improve medication adherence in patients with FH, starting in adolescents. An underused strategy to improve medication adherence incorporates the principles of behavioral economics. Traditional economic theory suggests that providing an incentive to perform a behavior will increase the frequency of that behavior. [However, two prominent theories in behavioral economics, Present Bias and Loss Aversion, suggest that not all types of incentives are effective and that poorly structured incentives can actually be negative enforcers. With novel mobile health technologies (mHealth), interventions based on behavioral economics can now be studied on a larger scale. In this proposal, the candidate 1) will test the efficacy of an mHealth intervention based on Present Bias and Loss Aversion to improve statin adherence in adolescents with FH in a randomized crossover trial; 2) gain a better understanding of the barriers to adherence in adolescents with risk factors for CVD using focus groups; and 3) perform a cost- effectiveness analysis with two-way sensitivity analysis of the interventions in Aim 1.] To achieve these goals and prepare for independence, a comprehensive career development program has been developed to gain additional training in: 1) clinical trials, 2) mHealth, 3) qualitative methods, 4) behavioral economics, and 5) cost- effectiveness analysis. Along with formal coursework, the candidate?s mentoring and advisory committee includes experts in FH and lifestyle interventions (Sarah de Ferranti), mHealth in CVD (Tiffany Powell-Wiley), cost-effectiveness analysis (Mihail Samnaliev), biostatistics and clinical trials (Kimberlee Gauvreau), internationally-known leaders in pediatric cardiology and clinical trials (Jane Newburger), and behavioral economics (Jason Doctor). Boston Children?s Hospital, Harvard School of Public Health, and the National Heart, Lung, and Blood Institute provide unparalleled environments to prepare a candidate for independence. Ultimately, the candidate?s long-term goals are to strengthen the understanding of factors that influence health behaviors in adolescence and to design cost-effective, personalized interventions to help reduce their risk for CVD. [The additional training and findings from this trial will be the basis for future R01 proposals that will expand this proposal to include multiple clinical sites with more diverse cohorts and to adolescents with other risk factors for CVD.]